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Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation.

Burguillos Garcia, Miguel LU ; Svensson, Martina LU ; Schulte, Tim ; Boza Serrano, Antonio LU ; Garcia-Quintanilla, Albert ; Kavanagh, Edel ; Santiago, Martiniano ; Viceconte, Nikenza ; Oliva-Martin, Maria Jose and Osman, Ahmed Mohamed , et al. (2015) In Cell Reports 10(9). p.1626-1638
Abstract
Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4) in microglia's inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3) released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection) and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that... (More)
Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4) in microglia's inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3) released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection) and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Reports
volume
10
issue
9
pages
1626 - 1638
publisher
Cell Press
external identifiers
  • pmid:25753426
  • wos:000350740300018
  • scopus:84924548953
  • pmid:25753426
ISSN
2211-1247
DOI
10.1016/j.celrep.2015.02.012
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuronal Survival (013212041), Pathology, (Lund) (013030000), Division of Microbiology, Immunology and Glycobiology - MIG (013025200), Neuroinflammation (013210006)
id
d42d59ef-b2f9-46b8-8066-b41ac268f5f6 (old id 5264939)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25753426?dopt=Abstract
date added to LUP
2016-04-01 14:29:57
date last changed
2020-09-23 04:42:06
@article{d42d59ef-b2f9-46b8-8066-b41ac268f5f6,
  abstract     = {Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4) in microglia's inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3) released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection) and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain.},
  author       = {Burguillos Garcia, Miguel and Svensson, Martina and Schulte, Tim and Boza Serrano, Antonio and Garcia-Quintanilla, Albert and Kavanagh, Edel and Santiago, Martiniano and Viceconte, Nikenza and Oliva-Martin, Maria Jose and Osman, Ahmed Mohamed and Salomonsson, Emma and Amar, Lahouari and Persson, Annette and Blomgren, Klas and Achour, Adnane and Englund, Elisabet and Leffler, Hakon and Venero, Jose Luis and Joseph, Bertrand and Deierborg, Tomas},
  issn         = {2211-1247},
  language     = {eng},
  number       = {9},
  pages        = {1626--1638},
  publisher    = {Cell Press},
  series       = {Cell Reports},
  title        = {Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation.},
  url          = {https://lup.lub.lu.se/search/ws/files/4007996/8053215.pdf},
  doi          = {10.1016/j.celrep.2015.02.012},
  volume       = {10},
  year         = {2015},
}